Genetic evaluation and clinical management of subsequent pregnancies based on previous adverse obstetric history

To explore the genetic value and clinical management strategies for subsequent pregnancies in women with a history of adverse obstetric outcomes.

204 pregnant women with a history of adverse obstetric outcomes, including spontaneous abortions and/or offspring with developmental anomalies, were retrospectively enrolled. The subjects were categorized into four groups based on the adverse characteristics of previous obstetric histories: inborn developmental anomalies group (IDAG, n = 53), genetic anomalies group (GAG, n = 35), composite group (CG, n = 52), and unknown etiology group (UEG, n = 64). In the subsequent pregnancy, the following strategies were conducted: ① All the fetuses underwent standardized ultrasound screening; ② Invasive fetal prenatal diagnosis were performed, including karyotyping (n = 204), copy number variation sequencing (CNV-seq, n = 161) and whole exome sequencing (WES, n = 11); ③ Dynamic ultrasound assessments and clinical follow-ups of pregnancy outcomes ranging from six months to six years were carried; ④ Fetal outcomes and maternal clinical characteristics among the different groups were further compared.

① Mean maternal age was not significant among four groups, however, the median gravidity and the median number of spontaneous abortion in UEG were the highest (p < 0.05). ② 8.33% (17/204) fetal genetic anomalies in subsequent pregnancy were found with abnormal chromosomes and 13.04% (21/161) anomalies were found by CNV-seq, among which 12 were investigated additionally. However, no significant difference was in the detection rate (DR) of karyotypes or CNVs among four groups. ③ 13 (6.37%, 13/204) fetuses presented abnormal ultrasonic manifestations accompanied with CNVs or pathogenic genes, and the DR of 9.38% (6/64) in abnormal manifestations of UEG was the highest. ④ 17 (8.33%, 17/204) chose termination and the survivors' growth and development were normal in the follow-ups from six months to six years.

Prenatal genetic diagnosis should be recommended for all subsequent pregnancies of families with adverse obstetric history. In addition, dynamic ultrasound and follow-up management are essential for clinicians to optimize neonatal outcomes.